1887

Abstract

Adaptation to the acidic microenvironment, and adherence to mucosal epithelium, are essential for persistent colonization of the human stomach by . The expression of SabA, an adhesin implicated in the ability of to adhere to the host gastric epithelium, can be modulated by phase variation via slipped-strand mispairing in repetitive nucleotide tracts located in both the promoter region and the coding region. This study demonstrates the occurrence of phase variation at the locus within individual strains of , and among multiple isolates from a single patient. In addition, transcription of is repressed by the acid-responsive ArsRS two-component signal transduction system . Our results demonstrate that isogenic inactivation of the (/) histidine kinase locus results in a 10-fold SabA-dependent increase in adherence to gastric epithelial cells in strain J99 (contains an in-frame allele), but not in strain 26695 (out-of-frame allele). The combination of transcriptional regulation of the locus by the ArsRS two-component signal-transduction system and the generation of subpopulations harbouring alternate alleles by slipped-strand mispairing during chromosomal replication could permit to rapidly adapt to varying microenvironments or host immune responses. As a pathogen with a paucity of regulatory proteins, this dual regulation indicates that SabA expression is a tightly regulated process in infection.

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2008-08-01
2020-11-29
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